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Endocrine
Erschienen in: Endocrine 1/2015

01.09.2015 | Original Article

Autocrine effect of Zn2+ on the glucose-stimulated insulin secretion

verfasst von: Kira G. Slepchenko, Nigel A. Daniels, Aili Guo, Yang V. Li

Erschienen in: Endocrine | Ausgabe 1/2015

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Abstract

It is well known that zinc (Zn2+) is required for the process of insulin biosynthesis and the maturation of insulin secretory granules in pancreatic beta (β)-cells, and that changes in Zn2+ levels in the pancreas have been found to be associated with diabetes. Glucose-stimulation causes a rapid co-secretion of Zn2+ and insulin with similar kinetics. However, we do not know whether Zn2+ regulates insulin availability and secretion. Here we investigated the effect of Zn2+ on glucose-stimulated insulin secretion (GSIS) in isolated mouse pancreatic islets. Whereas Zn2+ alone (control) had no effect on the basal secretion of insulin, it significantly inhibited GSIS. The application of CaEDTA, by removing the secreted Zn2+ from the extracellular milieu of the islets, resulted in significantly increased GSIS, suggesting an overall inhibitory role of secreted Zn2+ on GSIS. The inhibitory action of Zn2+ was mostly mediated through the activities of KATP/Ca2+ channels. Furthermore, during brief paired-pulse glucose-stimulated Zn2+ secretion (GSZS), Zn2+ secretion following the second pulse was significantly attenuated, probably by the secreted endogenous Zn2+ after the first pulse. Such an inhibition on Zn2+ secretion following the second pulse was completely reversed by Zn2+ chelation, suggesting a negative feedback mechanism, in which the initial glucose-stimulated Zn2+ release inhibits subsequent Zn2+ secretion, subsequently inhibiting insulin co-secretion as well. Taken together, these data suggest a negative feedback mechanism on GSZS and GSIS by Zn2+ secreted from β-cells, and the co-secreted Zn2+ may act as an autocrine inhibitory modulator.
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Metadaten
Titel
Autocrine effect of Zn2+ on the glucose-stimulated insulin secretion
verfasst von
Kira G. Slepchenko
Nigel A. Daniels
Aili Guo
Yang V. Li
Publikationsdatum
01.09.2015
Verlag
Springer US
Erschienen in
Endocrine / Ausgabe 1/2015
Print ISSN: 1355-008X
Elektronische ISSN: 1559-0100
DOI
https://doi.org/10.1007/s12020-015-0568-z

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